N-{3-[(3',5'-difluoro-1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide hydrochloride | 1124219-60-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-{3-[(3',5'-difluoro-1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide hydrochloride
• 英文别名: N-[3-[[4-(3,5-difluorophenyl)phenyl]methoxy]phenyl]piperidine-4-carboxamide;hydrochloride
• CAS: 1124219-60-8
• 化学式: C₂₅H₂₄F₂N₂O₂*ClH
• 分子量: 458.936
• InChiKey: GXALGLFTBQMWGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  50.4
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{3-[(3',5'-difluoro-1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide hydrochloride 在 potassium chloride 、 silver nitrate 、 三乙胺 作用下， 以 aq. phosphate buffer 、 二氯甲烷 、 乙腈 为溶剂， 生成 N-{3-[(3',5'-difluoro-1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide
  参考文献：
  名称：

  具有血管舒张和抗血小板活性的新的含机硝酸盐的有机硝酸酯

  摘要：

  通过将含硝酸盐的部分接枝到已被报道为中度有效的抗血小板药的苄氧基异壬基苯甲酰苯胺衍生物1和2的结构上，合成了许多新的一氧化氮（NO）前体。通过氨基甲酸酯和酰胺键将各种硝基氧基（ONO 2）-烷基侧链共价连接到母体化合物的哌啶氮上，并且还实现了化合物1的硝酸苄基酯类似物（15）的合成。评估了新合成的有机硝酸盐的体外血管舒张活性以及血小板的抗聚集作用。（ONO 2）氨基甲酸甲酯基衍生物5a另一方面，硝酸苄酯类似物15保留作为ADP诱导的血小板聚集抑制剂的活性，对预收缩的大鼠主动脉条显示出强烈的NO介导的血管舒张作用，EC 50值在低纳摩尔范围内（13和分别为29 nM）。用选择性抑制的可溶性鸟苷酸环化酶（s GC）（是NO介导的导致血管平滑肌松弛的途径的关键酶）进行的实验证实，NO参与了观察到的血管舒张。硝酸盐衍生物在酸性水溶液中和pH 7.4下均稳定。在人血清中，与5a不同，后者没有显示出酶催化的分解作用，另一种经过测试（ONO

  DOI：

  10.1016/j.ejps.2015.03.004
• 作为产物：
  描述：

  在 盐酸 作用下， 以 氯仿 为溶剂， 生成 N-{3-[(3',5'-difluoro-1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  Fluorinated Benzyloxyphenyl Piperidine-4-carboxamides with Dual Function against Thrombosis: Inhibitors of Factor Xa and Platelet Aggregation

  摘要：

  A series of benzyloxy anilides of nipecotic (5, 6) and isonipecotic (7, 8) acids were synthesized and assayed in vitro as inhibitors of ADP-induced platelet aggregation and the blood coagulation enzymes factor Xa (FXa) and thrombin (FIIa). An exploration of effects of the amidine group attached at the piperidine nitrogen,position and substitution (F, phenyl) of the benzyloxy group, and addition of fluorine/s on the second (distal) phenyl ring, led us to single out some promising isonipecotamide derivatives 7. Addition of meta-F and para-CF3 on the distal phenyl ring resulted in a 6-to-18-fold enhancement of the FXa potency and in 2-to-4-fold increase of the antiplatelet potency, the last depending to a large extent upon lipophilicity. Two congeners of N-{[3-(1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide (7m and 7p) proved to be potent FXa-selective inhibitors (K-i = 130 and 57 nM, respectively) and antiplatelet agents and were identified as leads for developing new dual function antithrombotic drugs.

  DOI：

  10.1021/jm801141f

文献信息

• New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity
  作者：Modesto de Candia、Elisabetta Marini、Giorgia Zaetta、Saverio Cellamare、Antonella Di Stilo、Cosimo D. Altomare

  DOI：10.1016/j.ejps.2015.03.004

  日期：2015.5

  a benzyl nitrate analog (15) of compound 1 was also achieved. The in vitro vasodilatory activities, as well as platelet anti-aggregatory effects, of the newly synthesized organic nitrates were assessed. The (ONO2)methyl carbamate-based derivative 5a and the benzyl nitrate analog 15, which on the other hand retain activity as inhibitors of ADP-induced platelet aggregation, exhibited strong NO-mediated

  通过将含硝酸盐的部分接枝到已被报道为中度有效的抗血小板药的苄氧基异壬基苯甲酰苯胺衍生物1和2的结构上，合成了许多新的一氧化氮（NO）前体。通过氨基甲酸酯和酰胺键将各种硝基氧基（ONO 2）-烷基侧链共价连接到母体化合物的哌啶氮上，并且还实现了化合物1的硝酸苄基酯类似物（15）的合成。评估了新合成的有机硝酸盐的体外血管舒张活性以及血小板的抗聚集作用。（ONO 2）氨基甲酸甲酯基衍生物5a另一方面，硝酸苄酯类似物15保留作为ADP诱导的血小板聚集抑制剂的活性，对预收缩的大鼠主动脉条显示出强烈的NO介导的血管舒张作用，EC 50值在低纳摩尔范围内（13和分别为29 nM）。用选择性抑制的可溶性鸟苷酸环化酶（s GC）（是NO介导的导致血管平滑肌松弛的途径的关键酶）进行的实验证实，NO参与了观察到的血管舒张。硝酸盐衍生物在酸性水溶液中和pH 7.4下均稳定。在人血清中，与5a不同，后者没有显示出酶催化的分解作用，另一种经过测试（ONO
• Fluorinated Benzyloxyphenyl Piperidine-4-carboxamides with Dual Function against Thrombosis: Inhibitors of Factor Xa and Platelet Aggregation
  作者：Modesto de Candia、Francesco Liantonio、Andrea Carotti、Raimondo De Cristofaro、Cosimo Altomare

  DOI：10.1021/jm801141f

  日期：2009.2.26

  A series of benzyloxy anilides of nipecotic (5, 6) and isonipecotic (7, 8) acids were synthesized and assayed in vitro as inhibitors of ADP-induced platelet aggregation and the blood coagulation enzymes factor Xa (FXa) and thrombin (FIIa). An exploration of effects of the amidine group attached at the piperidine nitrogen,position and substitution (F, phenyl) of the benzyloxy group, and addition of fluorine/s on the second (distal) phenyl ring, led us to single out some promising isonipecotamide derivatives 7. Addition of meta-F and para-CF3 on the distal phenyl ring resulted in a 6-to-18-fold enhancement of the FXa potency and in 2-to-4-fold increase of the antiplatelet potency, the last depending to a large extent upon lipophilicity. Two congeners of N-[3-(1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide (7m and 7p) proved to be potent FXa-selective inhibitors (K-i = 130 and 57 nM, respectively) and antiplatelet agents and were identified as leads for developing new dual function antithrombotic drugs.